crossing96/oncoscreening huggingface dataset:
Preoperative Cell-Free DNA (cfDNA) in Muscle-Invasive Bladder Cancer Treatment Outcome.	BACKGROUND: Tumor heterogeneity and lack of personalized prognosis leads to bladder cancer (BlCa) patients' lifelong surveillance with invasive interventions, highlighting the need for modern minimally invasive tools for disease management. Herein, we have evaluated the clinical utility of preoperative serum cell-free DNA (cfDNA) in ameliorating patients' risk-stratification and prognosis. METHODS: cfDNA was purified from 190 preoperative BlCa patients and 26 healthy individuals' serum samples and quantified by 2 assays: an in-house quantitative real-time PCR (qPCR) assay using LEP as reference control and a direct fluorometric assay using Qubit HS dsDNA. Capillary electrophoresis was performed in 31 samples for cfDNA fragment profiling. Tumor relapse/progression and metastasis/death were used as clinical endpoints for non-muscle-invasive bladder cancer and muscle-invasive bladder cancer (MIBC), respectively. RESULTS: cfDNA profiling by capillary electrophoresis highlighted that total and fragment-related cfDNA levels were significantly increased in BlCa and associated with advance disease stages. Evaluation of cfDNA levels by both Qubit/qPCR displayed highly consistent results (rs = 0.960; P < 0.001). Higher cfDNA was correlated with MIBC and stronger risk for early metastasis (Qubit:hazard ratio [HR] = 3.016, P = 0.009; qPCR:HR = 2.918, P = 0.004) and poor survival (Qubit:HR = 1.898, P = 0.042; qPCR:HR = 1.888, P = 0.026) of MIBC patients. Multivariate cfDNA-fitted models led to superior risk stratification and net benefit for MIBC prognosis compared to disease established markers. CONCLUSIONS: Elevated preoperative cfDNA levels are strongly associated with higher risk for short-term metastasis and poor outcome of MIBC, supporting modern noninvasive disease prognosis and management.	bladder
A novel bidirectional perfusion-like administered system for NIR-II fluorescence imaging precision diagnosis of bladder cancer.	Intravesical instillation has been considered an efficient route for detecting bladder cancer. However, only a small fraction of administered dose permeates into tumor tissues, and insufficient retention time limits their application. In this work, a novel intravesical bidirectional perfusion-like administered mode was developed to improve diagnostic accuracy of bladder tumor imaging. Specifically, the ultrasmall AuPd-P-FA Nanoprobe exhibit excellent NIR-II FL imaging performance due to electronic structure perturbation. Benefiting from the size advantage for kidney metabolism and FA targeting specificity, AuPd-P-FA could effectively administration to bladder tumor. When AuPd-P-FA reached maximum enrichment at 1 h post-injection, the localized and mild thermal energy produced upon laser irradiation activated a phase transition. This thermo-sensitive characteristic could prolong the retention time in bladder and the fluorescence signal could be clearly observed at 6 h post-injection with high accuracy. This novel intravesical bidirectional perfusion-like administered mode is expected to achieve a non-invasive diagnosis of early bladder cancer.	bladder
Immune-inflammatory-nutritional status predicts oncologic outcomes after radical cystectomy for urothelial carcinoma of bladder.	"OBJECTIVE: To perform the first investigation of the role of immune-inflammatory-nutritional status (INS) on oncological outcomes in patients undergoing open radical cystectomy (ORC) for urothelial carcinoma (UC). MATERIALS AND METHODS: The records of consecutive patients who underwent ORC for non-metastatic bladder cancer between 2009 and 2020 were retrospectively analyzed. Neoadjuvant chemotherapy, non-urothelial tumor biology, and absence of oncological follow-up were exclusion criteria. Systemic immune-inflammatory index (SII) and Prognostic Nutritional Index (PNI) values were calculated and optimal cut-off values for these were used to designate four subgroups: ""high SII-high PNI"", ""low SII-high PNI"", ""low SII-low PNI"", and ""high SII-low PNI"". The Low SII-high PNI INS group had best overall survival (OS) rate while the remainder were included in non-favorable INS group. Survival curves were constructed, and a multivariate Cox regression model was used for OS and recurrence-free survival (RFS). RESULTS: After exclusions, the final cohort size was 173 patients. The mean age was 64.31 ± 8.35 and median follow-up was 21 (IQR: 9-58) months. Optimal cut-off values for SII and PNI were 1216 and 47, respectively. The favorable INS group (low SII-high PNI, n = 89) had the best OS rate (62.9%). Multivariate Cox regression analysis indicated that non-favorable INS (n = 84) was a worse independent prognostic factor for OS (HR: 1.509, 95%CI: 1.104-3.145, p = 0.001) and RFS (HR: 1.285; 95%CI: 1.009-1.636, p = 0.042). CONCLUSION: Preoperative assessment of INS may be a useful prognostic panel for OS and RFS in patients who had ORC for UC."	bladder
Immunotherapy in Genitourinary Cancers: Role of Surgical Pathologist for Detection of Immunooncologic Predictive Factors.	Genitourinary malignancies include a broad spectrum of distinct tumor entities occurring in the kidney, the urinary tract, the prostate, the adrenal glands, the penis, and testicles. Each tumor entity presents with unique biological characteristics, especially in terms of immunobiology. The immune landscape of genitourinary malignancies differs between immunoreactive tumors like urothelial carcinoma or carcinomas of the kidney, for which several immunotherapeutic treatment options have been approved in the past years. In contrast, prostate cancer presents with low immunogenicity and previous trials exploring immune checkpoint inhibitors and other immunotherapeutic agents did not proof substantial survival benefits. In this review, we are presenting a streamlined overview on the role of surgical pathologists within the contemporary practice of immune oncology. It includes current indications for pathologic programmed death-ligand 1 (PD-L1) assessment and important pathologic considerations on PD-L1 testing harmonization including interassay and algorithm variabilities. In addition, we will discuss emerging biomarkers beyond PD-L1 and their potential to predict immunotherapy responses including tumor mutational burden, microsatellite instability, gene expression signatures, and histologic factors.	bladder
Preoperative upper tract invasive diagnostic modalities are associated with intravesical recurrence following surgery for upper tract urothelial carcinoma: A population-based study.	BACKGROUND: Intravesical recurrence (IVR) after surgery for upper tract urothelial carcinoma (UTUC) is a clinical problem. We investigated if preoperative invasive diagnostic modalities (IDM) such as antegrade/retrograde uretero-pyelography and/or selective urine cytology/barbotage, and URS with or without concomitant biopsy are associated with IVR after radical surgery for UTUC. Risk of death from urothelial cancer and all causes was investigated as secondary outcomes. METHODS: We investigated a population-based cohort of 1038 consecutive patients subjected to radical surgery for UTUC 2015-2019 in Sweden, using the Bladder Cancer Data Base Sweden (BladderBaSe 2.0), comprising all patients in the Swedish National Registry of Urinary Bladder Cancer. Risk estimates of IVR, death from urothelial cancer, and all causes was assessed using multivariable Cox regression models. RESULTS: The study included 536 cases with and 502 without preoperative IDM. IDM was associated with increased risk of IVR (HR 1.24, 95% CI 1.03-1.52) and risk of urothelial cancer death (HR 1.56, CI 1.12-2.18), compared to no IDM after a median follow-up of 1.3 yrs. Stratified analysis for tumor location showed that IDM was associated with risk of IVR in ureteric cancer (HR 1.66, 95% CI 1.21-2.28) but not in renal pelvic cancer (HR 1.07, 95% CI 0.81-1.41). Limitations included the observational setting and the lack of variables such as tumour grade, multifocality and preoperative hydronephrosis. CONCLUSIONS: Worse outcomes for patients subjected to preoperative IDM highlight the need for carefully considering diagnostic decisions for UTUC patients, specifically in tumours located in the ureter.	bladder
Efficacy and Feasibility of Presurgical Exercise in Bladder Cancer Patients Scheduled for Open Radical Cystectomy.	PURPOSE: This study aimed to examine the feasibility and potential efficacy of presurgical exercise in patients with bladder cancer scheduled for open radical cystectomy with follow-up postsurgery. METHODS: Prospective single-group design with assessments at baseline, presurgery, and 3 months postsurgery was used in this study. Multimodal supervised resistance and aerobic exercise was undertaken 2-3 d·wk -1 at moderate intensity for a median of 3.5 wk (interquartile range [IQR] = 1.3-5.6). Feasibility was assessed by recruitment and completion rates, patient safety, program tolerance, adherence, and compliance. Lean and fat mass were assessed by dual-energy x-ray absorptiometry, physical function by a battery of tests (chest press and leg press strength, 6-min walk test [6MWT], timed up-and-go, repeated chair rise), and quality of life (QoL), psychological distress, and body image by questionnaire. Hospital length of stay (LOS) and complications were assessed by medical records. RESULTS: Thirty-seven patients were referred with 20 recruited (67.3 ± 12.2 yr) and a presurgery intervention completion rate of 80% (16 of 20). The individual median program adherence was 100.0% (IQR = 89.4-100.0) with compliance of 100.0% (IQR = 90.5-100.0) for resistance exercise and 81.8% (IQR = 55.0-99.5) for aerobic exercise. There were no exercise-related adverse events. Body composition did not change presurgery; however, there were improvements ( P < 0.05) in leg press strength (16%), 6MWT distance (8%), timed up-and-go (12%), chair rise (10%), and multiple QoL domains including mental health. Median LOS was 8.0 d (IQR = 7.0, 15.0). Postsurgery, there were declines in components of QoL and apparent body image dissatisfaction. CONCLUSIONS: A preradical cystectomy exercise program is feasible, safe, and well tolerated with improvements in physical function and QoL. Supervised multimodal exercise in bladder cancer patients before cystectomy can enhance physical and mental health potentially buffering the effects of surgery.	bladder
Characterisation of tumour-immune phenotypes and PD-L1 positivity in squamous bladder cancer.	AIMS: Immune checkpoint inhibitor (ICI) therapy has become a viable treatment strategy in bladder cancer. However, treatment responses vary, and improved biomarkers are needed. Crucially, the characteristics of immune cells remain understudied especially in squamous differentiated bladder cancer (sq-BLCA). Here, we quantitatively analysed the tumour-immune phenotypes of sq-BLCA and correlated them with PD-L1 expression and FGFR3 mutation status. METHODS: Tissue microarrays (TMA) of n = 68 non-schistosomiasis associated pure squamous cell carcinoma (SCC) and n = 46 mixed urothelial carcinoma with squamous differentiation (MIX) were subjected to immunohistochemistry for CD3, CD4, CD8, CD56, CD68, CD79A, CD163, Ki67, perforin and chloroacetate esterase staining. Quantitative image evaluation was performed via digital image analysis. RESULTS: Immune infiltration was generally higher in stroma than in tumour regions. B-cells (CD79A) were almost exclusively found in stromal areas (sTILs), T-lymphocytes and macrophages were also present in tumour cell areas (iTILs), while natural killer cells (CD56) were nearly missing in any area. Tumour-immune phenotype distribution differed depending on the immune cell subset, however, hot tumour-immune phenotypes (high density of immune cells in tumour areas) were frequently found for CD8 + T-cells (33%), especially perforin + lymphocytes (52.2%), and CD68 + macrophages (37.6%). Perforin + CD8 lymphocytes predicted improved overall survival in sq-BLCA while high PD-L1 expression (CPS ≥ 10) was significantly associated with higher CD3 + , CD8 + and CD163 + immune cell density and high Ki67 (density) of tumour cells. Furthermore, PD-L1 expression was positively associated with CD3 + /CD4 + , CD3 + /CD8 + and CD68 + /CD163 + hot tumour-immune phenotypes. FGFR3 mutation status was inversely associated with CD8 + , perforin + and CD79A + lymphocyte density. CONCLUSIONS: Computer-based image analysis is an efficient tool to analyse immune topographies in squamous bladder cancer. Hot tumour-immune phenotypes with strong PD-L1 expression might pose a promising subgroup for clinically successful ICI therapy in squamous bladder cancer and warrant further investigation.	bladder
m6A writer WTAP targets NRF2 to accelerate bladder cancer malignancy via m6A-dependent ferroptosis regulation.	Recent evidence have indicated that ferroptosis, a novel iron-dependent form of non-apoptotic cell death, plays a critical role in human cancers. Besides, emerging literatures have revealed the ovel function of N(6)-methyladenosine (m(6)A) in bladder cancer physiological. However, the underlying mechanism of m(6)A on bladder cancer is still unclear. Here, present work revealed that m(6)A methyltransferase ('writer') WTAP up-regulated in bladder cancer tissue and cells, indicating the poor prognosis of bladder cancer patients. Functionally, gain/loss-of-functional experiments illustrated that WTAP promoted the viability of bladder cancer cells and inhibited the erastin-induced ferroptosis. Mechanistically, there was a remarkable m(6)A modification site on 3'-UTR of endogenous antioxidant factor NRF2 RNA and WTAP could install its methylation. Moreover, m(6)A reader YTHDF1 recognized the m(6)A site on NRF2 mRNA and enhanced its mRNA stability. Therefore, these findings demonstrated potential therapeutic strategyies for bladder cancer via m(6)A-dependent manner.	bladder
A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study.	BACKGROUND: Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients. OBJECTIVE: To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). DESIGN, SETTING, AND PARTICIPANTS: A multicenter phase 1 trial was conducted at community and academic sites. INTERVENTION: Patients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-treatment cystoscopy and urine cytology were performed at 3 and 6 -mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates. RESULTS AND LIMITATIONS: Twenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients. CONCLUSIONS: D combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches. PATIENT SUMMARY: Durvalumab combination therapy can be safely administered to non-muscle-invasive bladder cancer patients with the goal of increasing durable response rates.	bladder
A prognostic model based on necroptosis-related genes for prognosis and therapy in bladder cancer.	Bladder cancer, one of the most prevalent malignant cancers, has high rate of recurrence and metastasis. Owing to genomic instability and high-level heterogeneity of bladder cancer, chemotherapy and immunotherapy drugs sensitivity and lack of prognostic markers, the prognosis of bladder cancer is unclear. Necroptosis is a programmed modality of necrotic cell death in a caspase-independent form. Despite the fact that necroptosis plays a critical role in tumor growth, cancer metastasis, and cancer patient prognosis, necroptosis-related gene sets have rarely been studied in bladder cancer. As a result, the development of new necroptosis-related prognostic indicators for bladder cancer patients is critical. Herein, we assessed the necroptosis landscape of bladder cancer patients from The Cancer Genome Atlas database and classified them into two unique necroptosis-related patterns, using the consensus clustering. Then, using five prognosis-related genes, we constructed a prognostic model (risk score), which contained 5 genes (ANXA1, DOK7, FKBP10, MAP1B and SPOCD1). And a nomogram model was also developed to offer the clinic with a more useful prognostic indicator. We found that risk score was significantly associated with clinicopathological characteristics, TIME, and tumor mutation burden in patients with bladder cancer. Moreover, risk score was a valid guide for immunotherapy, chemotherapy, and targeted drugs. In our study, DOK7 was chosen to further verify our prognosis model, and functional assays indicated that knockdown the expression of DOK7 could prompt bladder cancer proliferation and migration. Our work demonstrated the potential role of prognostic model based on necroptosis genes in the prognosis, immune landscape and response efficacy of immunotherapy of bladder cancer.	bladder
Determination of potential sources of heavy metals in patients with urothelial carcinoma in central Taiwan: a biomonitoring case-control study.	The clarification of possible exposure sources of multiple metals to identify associations between metal doses and urothelial carcinoma (UC) risk is currently limited in the literature. We sought to identify the exposure sources of 10 metals (Vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, cadmium, and lead) using principal component analysis (PCA) and then linked various principal component (PC) scores with environmental characteristics, including smoking-related indices, PM(2.5), and distance to the nearest bus station. In addition, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA hypomethylation markers (5-methyl-2'-deoxycytidine levels; %5-MedC) were investigated in combination with UC risks. We conducted this hospital-based case control study in 359 UC patients with histologically confirmed disease and 718 controls. All data were collected from face-to-face interviews and medical records. Approximately 6 mL blood was collected from participants for analysis of multiple heavy metal and DNA methylation in leukocyte DNA. Further, a 20 mL urine sample was collected to measure urinary cotinine and 8-OHdG levels. In addition, average values for PM(2.5) for individual resident were calculated using the hybrid kriging/land-use regression model. In UC patients, significantly higher cobalt, nickel, copper, arsenic, and cadmium (μg/L) levels were observed in blood when compared with controls. Three PCs with eigenvalues > 1 accounted for 24.3, 15.8, and 10.7% of UC patients, and 26.9, 16.7, and 11.1% of controls, respectively. Environmental metal sources in major clusters were potentially associated with industrial activities and traffic emissions (PC1), smoking (PC2), and food consumption, including vitamin supplements (PC3). Multiple metal doses were linked with incremental urinary 8-OHdG and DNA hypomethylation biomarkers. For individuals with high PC1 and PC2 scores, both displayed an approximate 1.2-fold risk for UC with DNA hypomethylation.In conclusion, we provide a foundation for health education and risk communication strategies to limit metal exposure in environment, so that UC risks can be improved potentially.	bladder
News in the classification of WHO 2022 bladder tumors.	The fifth-edition of World Health Organization (WHO) Classification of Tumors series for urinary and male genital tract tumors has been published, six years later the fourth-edition. In these years, new treatment approaches have been implemented and new molecular data on urological cancers are known. Morphology remains the groundwork for taxonomy of the urinary tract tumors. However, a molecular approach to classification of urothelial carcinomas and the management of selected neoplasms with new therapeutic modalities such as immunotherapy are emerging. More data are needed for the application of these advances in routine pathology practice and patient management. The 2022 World Health Organization (WHO) Classification of Tumors of the Urinary System and Male Genital Organs represents an update in classification on urinary tract tumors. It also offers new insights with regards to the grading of heterogeneous non-invasive urothelial neoplasms, the definition of inverted neoplasms, the grading of invasive urothelial carcinomas, the diversity of morphological appearance of urothelial carcinomas, the definition of precursor lesions and the lineage of differentiation of the tumors.	bladder
The emerging role of cell cycle protein p53 expression by tumor cells and M2-macrophage infiltration in urinary bladder cancer.	PURPOSE: To investigate the association between p53 expression in tumor cells and intratumoral macrophage infiltration in muscle-invasive urinary bladder cancer (MIBC) in relation to clinical and pathological variables and outcomes after radical cystectomy. METHODS: Tumor specimens of the primary tumor from patients treated with radical cystectomy for MIBC were immunostained with the M2-macrophage-specific marker CD163 and the cell cycle protein p53. The expression of these markers was analyzed in relation to patients´ and tumor characteristics and outcome. RESULTS: Out of 100 patients with urinary bladder cancer (UBC) pathological stage T1-4 N0-3 M0, 77% were men. The patients had a median age of 69 years and 80% had nonorgan-confined tumors (pT3-4). Lymph node metastasis was found in 42 (42%) of all patients. P53-positive expressions were found in 63 (63%) patients. Strong macrophage infiltration in the tumor microenvironment was shown in 74 (74%) patients. Combinations of CD163/p53 status were as follows: CD163+/p53+, 50%; CD163+/p53-, 24%; CD163-/p53+, 13%; and CD163-/p53-, 13%. Patients with CD163+/P53+ had higher proportions of organ-confined tumors. CONCLUSIONS: In the present series of patients with MIBC treated with cystectomy, we found that high CD163+ macrophage infiltration in the tumor micro-environment often was combined with p53+ cancer cells. This simultaneous expression of p53 by tumor cells and increased infiltration of M2-macrophages in the tumor microenvironment was associated with improved CSS, which might indicate a possible protective effect of M2 macrophages in p53+ tumors. Further investigations are needed to explore the biological relation between mutational burden and immune profile in MIBC.	bladder